tbuckley/cabot-search huggingface dataset:
Novel CD19-specific γ/δ TCR-T cells in relapsed or refractory diffuse large B-cell lymphoma
Authors: Chenggong Li, Fen Zhou, Jing Wang, Qi Chang, Mengyi Du, Wenjing Luo, Yinqiang Zhang, Jia Xu, Lu Tang, Huiwen Jiang, Lin Liu, Haiming Kou, Cong Lu, Danying Liao, Jianghua Wu, Qiuzhe Wei, Sha Ke, Jun Deng, Cheng Liu, Heng Mei, Yu Hu
Journal: Journal of Hematology & Oncology (2023)

Abstract Background T cell receptor (TCR)-T cells possess similar effector function, but milder and more durable signal activation compared with chimeric antigen receptor-T cells. TCR-T cell therapy is another active field of cellular immunotherapy for cancer. Methods We previously developed a human anti-CD19 antibody (ET190L1) and generated novel CD19-specific γ/δ TCR-T cells, ET019003, by fusing the Fab fragment of ET190L1 with γ/δ TCR constant chain plus adding an ET190L1-scFv/CD28 co-stimulatory molecule. ET019003 cells were tested in preclinical studies followed by a phase 1 clinical trial. Results ET019003 cells produced less cytokines but retained comparable antitumor potency than ET190L1-CAR-T cells in vivo and in vitro. In the first-in-human trial, eight patients with relapsed or refractory DLBCL were treated. CRS of grade 1 was observed in three (37.5%) patients; ICANS of grade 3 was noted in one (12.5%) patient. Elevation of serum cytokines after ET019003 infusion was almost modest. With a median follow-up of 34 (range 6–38) months, seven (87.5%) patients attained clinical responses and six (75%) achieved complete responses (CR). OS, PFS and DOR at 3 years were 75.0%, 62.5%, and 71.4%, respectively. Notably, patient 1 with primary CNS lymphoma did not experience CRS or ICANS and got an ongoing CR for over 3 years after infusion, with detectable ET019003 cells in CSF. ET019003 showed striking in vivo expansion and persisted in 50% of patients at 12 months. Three patients received a second infusion, one for consolidation therapy after CR and two for salvage therapy after disease progression, but no response was observed. ET019003 expansion was striking in the first infusion, but poor in the second infusion. Conclusions CD19-specific γ/δ TCR-T cells, ET019003, had a good safety profile and could induce rapid responses and durable CR in patients with relapsed or refractory DLBCL, even primary CNS lymphoma, presenting a novel and potent therapeutic option for these patients. Trial registration : NCT04014894.
Primary myelofibrosis: 2023 update on diagnosis, risk‐stratification, and management
Authors: Ayalew Tefferi
Journal: American Journal of Hematology (2023)

Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by stem cell-derived clonal myeloproliferation that is often but not always accompanied by JAK2, CALR, or MPL mutations; additional features include bone marrow reticulin/collagen fibrosis, aberrant inflammatory cytokine expression, anemia, hepatosplenomegaly, extramedullary hematopoiesis (EMH), constitutional symptoms, cachexia, risk of leukemic progression, and shortened survival.Bone marrow examination with cytogenetic and mutation studies provides integrated diagnostic information; presence of JAK2, CALR or MPL mutation is expected but not required.The International Consensus Classification distinguishes "prefibrotic" from "overtly fibrotic" PMF; the former might mimic essential thrombocythemia (ET) in its presentation. Approximately 15% of patients with ET or polycythemia vera (PV) might progress into post-ET/PV MF.SRSF2, ASXL1, and U2AF1-Q157 mutations predict inferior survival in PMF; RAS/CBL mutations predict resistance to ruxolitinib therapy. Type 1/like CALR mutation is associated with superior survival.Very high-risk abnormalities include -7, inv (3), i(17q), +21, +19, 12p- and 11q-. Favorable risk abnormalities include normal karyotype or isolated +9, 13q-, 20q-, 1q abnormalities and loss of Y chromosome.Contemporary prognostic systems include GIPSS (genetically-inspired prognostic scoring system) and MIPSS70+ version 2.0 (MIPSSv2; mutation-and karyotype-enhanced international prognostic scoring system). GIPSS is based exclusively on mutations and karyotype; MIPSSv2 includes, in addition, clinical risk factors.Observation alone is advised for MIPSSv2 "low" and "very low" risk disease (estimated 10-year survival 56%-92%); allogeneic hematopoietic stem cell transplant (AHSCT) is the preferred treatment of choice for "very high" and "high" risk disease (estimated 10-year survival 0-13%), as well as in carefully selected patients with intermediate-risk disease (estimated 10-year survival 30%). Drug therapy in MF is currently palliative and targets anemia, splenomegaly, and constitutional symptoms. JAK2 INHIBITORS: Ruxolitinib, fedratinib, and pacritinib are FDA approved and respectfully utilized in patients failing treatment with hydroxyurea, ruxolitinib, or with platelet count <50 × 10 (9)/L. Momelotinib is another JAK2 inhibitor that is poised for approval sometime in 2023 and has shown erythropoietic benefits, in addition to affecting spleen and symptom responses.Splenectomy is considered for drug-refractory splenomegaly and involved field radiotherapy for non-hepatosplenic EMH and extremity bone pain.New agents, alone or in combination with ruxolitinib, are currently under clinical trial investigation (ClinicalTrials.gov) and preliminary results were presented at the 2022 ASH annual meeting and highlighted in the current review.
Associations between Serial Intravitreal Injections and Dry Eye
Authors: Agni Malmin, Vilde M. Thomseth, Per T. Førland, Ayyad Z. Khan, Hanne B. Hetland, Xiangjun Chen, Inga-Britt K. Haugen, Tor P. Utheim, Vegard A. Forsaa
Journal: Ophthalmology (2023)

PurposeTo investigate the effects of serial intravitreal injections (IVI) on the ocular surface and meibomian glands (MG) in patients treated with anti-vascular endothelial growth factor (anti-VEGF) for neovascular age-related macular degeneration (nAMD).DesignRetrospective controlled observational study.SubjectsPatients with nAMD receiving unilateral IVI with anti-VEGF agents. The fellow eye was used as control.MethodsTear film and ocular surface examinations were performed on a single occasion at a minimum of four weeks after IVI. A pre-IVI asepsis protocol with povidone-iodine was applied.Main Outcome MeasuresUpper and lower MG loss, tear meniscus height (TMH), bulbar redness score (BR), non-invasive tear break-up time (NIBUT), tear film osmolarity (TOsm), Schirmer test, corneal staining, fluorescein tear film break-up time (TBUT), meibomian gland expressibility (ME) and meibum quality (MQ).ResultsNinety patients with a mean age of 77.5 years (SD 8.4; range 54-95) were included. The median number of IVI in treated eyes was 19.5 (range 2–132). Mean MG loss in the upper eyelid was 19.1 (SD 11.3) % in treated eyes and 25.5 (SD 14.6) % in untreated fellow eyes (P=0.001). For the lower eyelid, median MG loss was 17.4 (IQR 9.4-29.9) % in treated eyes and 24.5 (IQR 14.2-35.2) % in fellow eyes (P<0.001). Mean BR was 1.32 (SD 0.46) in treated eyes versus 1.44 (SD 0.45) in fellow eyes (P=0.017). Median TMH was 0.36 (IQR 0.28-0.52) mm in treated eyes and 0.32 (IQR 0.24-0.49) mm in fellow eyes (P=0.02). There were no differences between treated and fellow eyes regarding NIBUT, TOsm, Schirmer test, corneal staining, fluorescein TBUT, meibomian gland expressibility ME or MQ.ConclusionsRepeated IVI with anti-VEGF with preoperative povidone-iodine application was associated with reduced meibomian gland loss, increased tear volume and reduced signs of inflammation compared to fellow non-treated eyes in patients with nAMD. This regimen may thus have a beneficial effect on the ocular surface.
Fast Progressors in Glaucoma
Authors: Aidan B. Jackson, Keith R. Martin, Michael A. Coote, Felipe A. Medeiros, Christopher A. Girkin, Massimo A. Fazio, Jeffrey M. Liebmann, Carlos Gustavo De Moraes, Robert N. Weinreb, Linda M. Zangwill, Zhichao Wu
Journal: Ophthalmology (2023)
BET inhibitors rescue anti-PD1 resistance by enhancing TCF7 accessibility in leukemia-derived terminally exhausted CD8+ T cells
Authors: Kyle A. Romine, Kevin MacPherson, Hyun-jun Cho, Yoko Kosaka, Patrick A. Flynn, Kaelan H. Byrd, Jesse L. Coy, Matthew T. Newman, Ravina Pandita, Christopher P. Loo, Jaime Scott, Andrew C. Adey, Evan F. Lind
Journal: Leukemia (2023)

Abstract Many acute myeloid leukemia (AML) patients exhibit hallmarks of immune exhaustion, such as increased myeloid-derived suppressor cells, suppressive regulatory T cells and dysfunctional T cells. Similarly, we have identified the same immune-related features, including exhausted CD8 + T cells (TEx) in a mouse model of AML. Here we show that inhibitors that target bromodomain and extra-terminal domain (BET) proteins affect tumor-intrinsic factors but also rescue T cell exhaustion and ICB resistance. Ex vivo treatment of cells from AML mice and AML patients with BET inhibitors (BETi) reversed CD8 + T cell exhaustion by restoring proliferative capacity and expansion of the more functional precursor-exhausted T cells. This reversal was enhanced by combined BETi and anti-PD1 treatment. BETi synergized with anti-PD1 in vivo, resulting in the reduction of circulating leukemia cells, enrichment of CD8 + T cells in the bone marrow, and increase in expression of Tcf7 , Slamf6 , and Cxcr5 in CD8 + T cells. Finally, we profiled the epigenomes of in vivo JQ1-treated AML-derived CD8 + T cells by single-cell ATAC-seq and found that JQ1 increases Tcf7 accessibility specifically in Tex cells, suggesting that BETi likely acts mechanistically by relieving repression of progenitor programs in Tex CD8 + T cells and maintaining a pool of anti-PD1 responsive CD8 + T cells.
Computing personalized brain functional networks from fMRI using self-supervised deep learning
Authors: Hongming Li, Dhivya Srinivasan, Chuanjun Zhuo, Zaixu Cui, Raquel E. Gur, Ruben C. Gur, Desmond J. Oathes, Christos Davatzikos, Theodore D. Satterthwaite, Yong Fan
Journal: Medical Image Analysis (2023)
The HoloLens in medicine: A systematic review and taxonomy
Authors: Christina Gsaxner, Jianning Li, Antonio Pepe, Yuan Jin, Jens Kleesiek, Dieter Schmalstieg, Jan Egger
Journal: Medical Image Analysis (2023)

The HoloLens (Microsoft Corp., Redmond, WA), a head-worn, optically see-through augmented reality (AR) display, is the main player in the recent boost in medical AR research. In this systematic review, we provide a comprehensive overview of the usage of the first-generation HoloLens within the medical domain, from its release in March 2016, until the year of 2021. We identified 217 relevant publications through a systematic search of the PubMed, Scopus, IEEE Xplore and SpringerLink databases. We propose a new taxonomy including use case, technical methodology for registration and tracking, data sources, visualization as well as validation and evaluation, and analyze the retrieved publications accordingly. We find that the bulk of research focuses on supporting physicians during interventions, where the HoloLens is promising for procedures usually performed without image guidance. However, the consensus is that accuracy and reliability are still too low to replace conventional guidance systems. Medical students are the second most common target group, where AR-enhanced medical simulators emerge as a promising technology. While concerns about human–computer interactions, usability and perception are frequently mentioned, hardly any concepts to overcome these issues have been proposed. Instead, registration and tracking lie at the core of most reviewed publications, nevertheless only few of them propose innovative concepts in this direction. Finally, we find that the validation of HoloLens applications suffers from a lack of standardized and rigorous evaluation protocols. We hope that this review can advance medical AR research by identifying gaps in the current literature, to pave the way for novel, innovative directions and translation into the medical routine.
Elevated Myocardial Cytosolic Calcium Impairs Insulin-Like Growth Factor-1-Stimulated Protein Synthesis in Chronic Renal Failure
Authors: DAVID PEIYUAN QING, HU DING, JAY VADGAMA, YAN YUAN WU, JOEL D. KOPPLE
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Rats and humans with chronic renal failure (CRF) are reported to have resistance to recombinant human insulin-like growth factor-1 (rhIGF-1). Because basal cytosolic calcium ([Ca 2+ ] i ), a second messenger, may be increased in CRF, this study was conducted to examine whether elevated basal [Ca 2+ ] i may cause resistance to IGF-1. Cardiomyocytes from four groups of rats were studied: untreated CRF, CRF with parathyroidectomy (PTX), CRF with the calcium channel blocker felodipine (F), and sham operation of the kidney (SO). CRF was created by ligation of two-thirds of the left renal artery and contralateral nephrectomy. Rats from each group were pair-fed the same diet for 20 to 22 d. Basal [Ca 2+ ] i in cardiomyocytes (nM) in the CRF rats (102.0 ± 2.8; SEM), was significantly higher than in each of the CRF-PTX, CRF-F, and SO groups (65.2 ± 1.9, 63.8 ± 2.6, and 63.5 ± 2.0, respectively; P &lt; 0.01). rhIGF-1 increased cardiomyocyte [Ca 2+ ] i in all four groups of rats. The rise in [Ca 2+ ] i was significantly diminished in the CRF rats ( P &lt; 0.05) and did not differ among the CRF-PTX, CRF-F, and SO rats. Protein synthesis after incubation with 0, 50, 100, 200, or 400 ng/ml rhIGF-1 was lower in cardiomyocytes from CRF rats than in each of the other three groups ( P &lt; 0.05) and was significantly less in the CRF-F rats compared with SO animals. IGF-1 receptor mRNA and IGF-1 receptor number and affinity were not different among the four groups. These findings suggest that cardiomyocytes from CRF rats display elevated basal [Ca 2+ ] i and attenuated rhIGF-1-induced increase in [Ca 2+ ] i ; basal protein synthesis is decreased, and IGF-1-stimulated protein synthesis is impaired; elevated basal [Ca 2+ ] i seems to contribute to this diminished response to rhIGF-1.
Aplastic Anemia and Viral Hepatitis
Authors: Jonathan R. Hibbs
Journal: JAMA (1992)

<h3>Objective.</h3> —To test the hypothesis that the rare, often fatal, syndrome of hepatitis-associated aplasia is associated with hepatitis C virus infection. <h3>Design.</h3> —Case series. <h3>Setting.</h3> —Tertiary referral centers in the United States, Japan, Italy, and Germany. <h3>Patients.</h3> —Twenty-eight patients with onset of aplastic anemia within 90 days after seeking medical attention for jaundice, or having serum transaminase levels 150% or more of normal (hepatitis-associated aplasia patients) and three patients who developed aplastic anemia following liver transplantation for non-A, non-B hepatitis. <h3>Outcome Measures.</h3> —Presence of hepatitis C in serum, bone marrow, and liver samples, detected by the polymerase chain reaction; antibody testing; and percentage of activated peripheral cytotoxic T lymphocytes determined by immunophenotyping. <h3>Results.</h3> —Hepatitis ribonucleic acid was present in the serum samples of 10 (36%) patients with hepatitis-associated aplasia. However, hepatitis C virus viremia was associated with transfusions received after the onset of aplasia: seven (58%) of 12 patients with hepatitis-associated aplasia who had received 21 or more units of blood products at the time of serum sampling were viremic, compared with only three (19%) of 16 patients with hepatitis-associated aplasia who had received 20 or less units of blood products (<i>P</i>&lt;.05). Hepatitis C virus was not found in blood and bone marrow samples of three National Institutes of Health case patients tested at the time of diagnosis. None of three livers from non-A, non-B hepatitis patients who developed aplastic anemia after liver transplantation contained hepatitis C virus ribonucleic acid. Activated CD8+ T lymphocytes were elevated three- to 20-fold early in the course of hepatitis-associated aplasia. <h3>Conclusions.</h3> —Our results implicate a novel, non-A, non-B, and non-C agent in both hepatitis-associated aplasia and fulminant hepatitis. (<i>JAMA</i>. 1992;267:2051-2054)
The Epidemiology of Disease Expenses
Authors: Bernard S. Bloom
Journal: JAMA (1985)

We determined medical costs and family out-of-pocket expenses over time for 569 children with malignant neoplasms. All medical charges (inpatient and outpatient), family out-of-pocket expenses, and wages lost were collected and annualized. The mean cost of cancer care and treatment per patient-year was $29,708, with variation by diagnosis, prognosis, and year since diagnosis. The mean annual hospital inpatient cost was $15,455; mean ambulatory care cost, $3,806; and family out-of-pocket disease-related expenses, $9,787. Family out-of-pocket expenses added about 50% to the total cost of disease-related care and consumed 38% of gross annual family income; wages lost accounted for nearly half. About 95% of all medical costs was paid by private, public, or charitable payers. Out-of-pocket medical expenses for which the family was responsible were about $1,000 each year. However, all nonmedical, disease-related expenses were borne by the family. (<i>JAMA</i>1985;253:2393-2397)
Small-bowel endoscopy
Authors: A. May
Journal: Endoscopy (2012)

In recent years, several studies have reported on an improvement in the visualization and classification of lesions in the upper and lower gastrointestinal tract using computed virtual chromoendoscopy (CVC), such as narrow-band imaging (NBI), flexible spectral imaging color inhancement (FICE) or i-Scan. CVC enhances the contrast of the mucosal surface without the use of dyes. The FICE system is based on narrowing of the bandwidth of the conventional endoscopic image arithmetically by a spectral estimation technology and enhances the vascular network as well as the pit pattern, facilitating the assessment of gastrointestinal mucosal lesions [2]. Neumann et al. described for the first time the use of double-balloon enteroscopy (DBE) and the FICE system for classification of small-bowel lesions in a case series [3]. FICE was found to be a helpful method for the evaluation of adenomatous small-bowel polyps and angiodysplasias [3].
Familial Hypobetalipoproteinemia
Authors: Jeffrey A. Kahn
Journal: JAMA (1978)

FAMILIAL hypobetalipoproteinemia is characterized by sharply reduced levels of plasma cholesterol and lowdensity lipoprotein cholesterol (C-LDL).<sup>1,2</sup>High-density lipoprotein cholesterol (C-HDL) level is normal to slightly elevated.<sup>2</sup>Men and women from hypobetalipoproteinemic kindreds had reported life expectancies that were seven and six years longer, respectively, than for US white populations (<i>P</i>&lt;.002).<sup>2</sup>Combined myocardial infarction morbidity and mortality was 2.5% in hypobetalipoproteinemic kindreds, fivefold less than in normolipemic controls (11%;<i>P</i>&lt;.01).<sup>2</sup>In hypobetalipoproteinemia, low C-LDL, the atherogenic lipoprotein,<sup>2-4</sup>or a low ratio of C-LDL to C-HDL, the antiatherogenic lipoprotein,<sup>2,4</sup>may facilitate longevity and decrease morbidity and mortality from myocardial infarction.<sup>2</sup> We report what to our knowledge is the first documented autopsy study of a patient with familial hypobetalipoproteinemia and in whom there were no arterial atherosclerotic lesions on either gross or microscopic examination. <h3>Report of a Case</h3> A 76-year-old woman was found to
Inhibition of Chemically Induced Mammary Carcinogenesis in Rats by Short-Term Exposure to Butylated Hydroxytoluene (BHT): Interrelationships Among BHT Concentration, Carcinogen Dose, and Diet234
Authors: L. A. Cohen, M. Polansky, K. Furuya, M. Reddy, B. Berke, J. H. Weisburger
Journal: JNCI Journal of the National Cancer Institute (1984)

Dietary butylated hydroxytoluene (BHT) fed 14 days before and 14 days after carcinogen administration resulted in a dose-dependent inhibition of 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumor incidence in outbred Sprague-Dawley rats. In addition, the inhibitory effects of BHT were strongly influenced by the dose of initiating carcinogen and the type of diet in which BHT was administered. In animals fed the NIH-07 diet and receiving a low dose of DMBA (5 mg/rat), the inhibitory effect of BHT was manifested at all four BHT concentrations (6,000→300 ppm). Maximal inhibition was approximately 50% in animals given 5 mg DMBA and receiving 6,000 ppm BHT. However, in the group administered a high dose of DMBA (15 mg/rat), the inhibitory effect of BHT was expressed only at 6,000 ppm, the highest concentration given. Lower concentrations (300 and 1,000 ppm) of BHT had no detectable effect on tumor incidence. In animals fed the defined, semi-purified AIN-76A diet during the 4-week treatment period and initiated with 5 mg DMBA, BHT at 6,000 ppm inhibited tumor development. However, at 15 mg DMBA animals fed the AIN-76A diet differed markedly from those fed the NIH-07 diet. In the former group, BHT at 6,000 ppm was unable to elicit any inhibitory response; in the latter group, BHT inhibited tumor development by 40%. Dietary BHT also inhibited DMBA-induced adrenocortical hyperplastic nodules in a dose-dependent fashion. These results indicate that short-term exposure to dietary BHT can inhibit experimental mammary tumor development at environmentally relevant concentrations.
Voluntary Risks to Health
Authors: Robert M. Veatch
Journal: JAMA (1980)

The discovery that health status is affected by personal life-styles and apparently voluntary health risks poses new problems. It has potential impact on clinical practice, health insurance, and theories of health and disease. Five major problems need attention. First, are these health-risk behaviors really voluntary? Five responses are explored: several other models (the medical, psychological, social structural, and multicausal models) all challenge the assumption of voluntary behavior. Second, are some sufficiently in the public interest that they ought to be subsidized? Third, does justice require that persons bear the costs of truly voluntary health risks? Fourth, what policies should apply to cost-saving, health-risk behavior? Finally, does the voluntary health-risks theme make life too rational and calculating? These issues must be dealt with in future health planning and clinical decision making. (<i>JAMA</i>243:50-55, 1980)
Clinical Decision Analysis
Authors: James C. Sisson
Journal: JAMA (1976)

Acquisition of laboratory data bearing on a clinical problem may make patient care worse rather than better. The hazards of obtaining new information, that go beyond the monetary costs and risks to physical well-being, are frequently not appreciated by physicians. In the complex and many-faceted practice of medicine, intuition, even when expressed by experienced clinicians, may lead to faulty judgments. Decision analysis gives a systematic exposition of clinical management, and lessens, if not eliminates, the influence of biased and unreliable intuition. With practice, most physicians could employ decision analysis to help solve moderately complicated problems at the bedside or in the office. Use of this tactic will make gaps in knowledge explicit, and may thereby stimulate investigations to ensure better clinical judgments in the future. (<i>JAMA</i>236:1259-1263, 1976)
Multiple Sclerosis and Hysteria
Authors: Louis R. Caplan
Journal: JAMA (1980)

Four patients with organic neurological disease (multiple sclerosis) had additional major hysterical disability. Patients with unequivocal organic disease often have coexistent psychological disturbances. The preexisting personality, nature of the organic disease and its disability, and the psychosocial setting interact and create an illness whose components are difficult to separate. In some patients there are definite secondary gains from an illness. The combination of hysteria and multiple sclerosis serves as a model for the coexistence of organic and psychological disorders; it serves as an example of the general questions of how the sick deal with their infirmities and how the physician comprehensively deals with illness. (<i>JAMA</i>243:2418-2421, 1980)